Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma

Haematologica. 2002 Aug;87(8):846-50.

Abstract

Background and objectives: Since optimal collection of peripheral blood progenitor cells (PBPC) remains crucial for high-dose therapy in patients with multiple myeloma (MM) in relapse phase or refractory to chemotherapy, we evaluated several variables that may influence mobilization.

Design and methods: Eighty-nine patients who underwent a standard mobilization procedure with cyclophosphamide (3 g/m2) and growth factors entered the study. A composite collection totalling at least 2x106 CD34+/kg was defined as a sufficient yield: 59 patients achieved an adequate collection. A reliable factor to predict adequate yields was prior therapy: an adequate collection was obtained in 92% of patients treated with conventional non-alkylating therapy (VAD-based regimens), in 56% treated with oral melphalan and in 23% who had received intravenous melphalan.

Results: The three groups were similar for most clinical features. After adjustment for several potential confounders, the probability of an adequate PBPC collection remained higher in the group treated with non-alkylating agents, with an odds ratio (OR) of 6.14 (95% confidence interval, CI=1.34, 28.13) and lower in those treated with intravenous melphalan (OR=0.08; CI=0.01-0.61), when compared to the group treated with oral melphalan. Among the other prognostic factors (stage, percentage of bone marrow plasma cells, b2-microglobulin, labeling index, isotype, monoclonal component, Bence-Jones proteinuria) evaluated at diagnosis, there was no clear association with progenitor cell yield.

Interpretation and conclusions: In conclusion, patients who are potential candidates for high-dose therapy with PBPC support should not receive conventional alkylating therapy, even orally. Alternatively, progenitor cells should be collected early in the course of MM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Blood Cell Count
  • Combined Modality Therapy
  • Contraindications
  • Cyclophosphamide / pharmacology
  • Dexamethasone / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Hematopoietic Stem Cell Mobilization* / methods
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Male
  • Melphalan / administration & dosage
  • Melphalan / pharmacology*
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / therapy
  • Odds Ratio
  • Retrospective Studies
  • Salvage Therapy
  • Stem Cell Transplantation
  • Vincristine / administration & dosage

Substances

  • Antineoplastic Agents, Alkylating
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Melphalan

Supplementary concepts

  • VAD protocol